Adutwum Michelle, Hurst Anna, Mirzaa Ghayda, Kushner Jessica D, Rogers Caleb, Khalek Nahla, Cristancho Ana G, Burrill Natalie, Seifert Michael E, Scarano Maria I, Schnur Rhonda E, Slavotinek Anne
Children's Hospital Oakland Research Institute Summer Program, University of California San Francisco, San Francisco, California, USA.
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Clin Genet. 2023 Jan;103(1):97-102. doi: 10.1111/cge.14222. Epub 2022 Sep 21.
The Crumbs homolog-2 (CRB2)-related syndrome (CRBS-RS) is a rarely encountered condition initially described as a triad comprising ventriculomegaly, Finnish nephrosis, and elevated alpha-fetoprotein levels in maternal serum and amniotic fluid. CRB2-related syndrome is caused by biallelic, pathogenic variants in the CRB2 gene. Recent reports of CRB2-RS have highlighted renal disease with persistent proteinuria and steroid-resistant nephrotic syndrome (SRNS). We report six new and review 28 reported patients with pathogenic variants in CRB2. We compare clinical features and variant information in CRB2 in patients with CRB2-RS and in those with isolated renal disease. The kidneys were the most frequently involved body system and 11 patients had only renal manifestations with SRNS or nephrotic syndrome. Central nervous system involvement was the next most common manifestation, followed by cardiac findings that included Scimitar syndrome. There was a significant clustering of pathogenic variants for CRB2-RS in exons 8 and 10, whereas pathogenic variants in exons 12 and 13 were associated with isolated renal disease. Further information is needed to determine optimal management but monitoring for renal and ocular complications should be considered.
Crumb 同源物 2（CRB2）相关综合征（CRBS-RS）是一种罕见病症，最初被描述为一种三联征，包括脑室扩大、芬兰型肾病以及母体血清和羊水中甲胎蛋白水平升高。CRB2 相关综合征由 CRB2 基因的双等位基因致病性变异引起。最近关于 CRB2-RS 的报道突出了伴有持续性蛋白尿和激素抵抗型肾病综合征（SRNS）的肾脏疾病。我们报告了 6 例新病例，并回顾了 28 例报道的携带 CRB2 致病性变异的患者。我们比较了 CRB2-RS 患者和孤立性肾脏疾病患者的临床特征及 CRB2 变异信息。肾脏是最常受累的身体系统，11 例患者仅有 SRNS 或肾病综合征的肾脏表现。中枢神经系统受累是第二常见的表现，其次是包括弯刀综合征在内的心脏表现。CRB2-RS 的致病性变异在外显子 8 和 10 中显著聚集，而外显子 12 和 13 中的致病性变异与孤立性肾脏疾病相关。需要更多信息来确定最佳治疗方案，但应考虑对肾脏和眼部并发症进行监测。
